# Spatiotemporal Dynamics of Noradrenergic Signaling in the Neocortex

> **NIH NIH F31** · YALE UNIVERSITY · 2022 · $46,752

## Abstract

Project Summary:
Noradrenaline is thought to mediate arousal and regulate the behavioral state of animals. In particular,
noradrenaline bidirectionally modifies mnemonic and sensory encoding, prioritizing neural resources for
imminent behavioral demands. Emerging evidence has suggested a capacity for spatially targeted noradrenergic
release, yet the field has lacked tools with sufficient spatiotemporal resolution to resolve this possibility. Cell type
specific sensitives to noradrenergic modulation underly the differing action of noradrenaline on mnemonic tuning
in the frontal cortex and stimulus encoding in primary visual and somatosensory cortices. However, the study of
isolated brain regions has precluded a holistic view of noradrenergic modulation across the cortex. Furthermore,
how noradrenergic modulation of cortex-wide networks emerges from the level of single cells is virtually
unexplored. Leveraging a recently developed technique from our lab to image the release of neuromodulators
with high spatiotemporal resolution across the entirety of the dorsal-cortex, we have begun to characterize the
spatiotemporal specificity of noradrenergic release and its relation to neural activity. Our preliminary data shows
noradrenergic release is spatially homogenous and associated with distinct behavioral states. We further find
the coupling of noradrenergic release to be spatiotemporally heterogenous, implicating noradrenaline in the
engagement of distinct cortex-wide networks. To further pursue our preliminary data, we propose simultaneous
application of several methodological approaches: 1 photon widefield “mesoscopic” dual channel imaging, local
pharmacological infusions, and extracellular electrophysiological recordings with high density silicon probes. Our
combinatorial approach will allow us to test the following hypothesis: (1) noradrenergic release is spatially
homogenous but temporally heterogenous, with noradrenergic release associated with some behavioral states
but not others. (2) Noradrenergic release is heterogeneously coupled with local neural activity through α2a
receptors and prone to behavioral state dependent regulation. (3) Noradrenaline modulates the coupling of single
cells to large-scale cortical networks in a state dependent manner. Our results will provide an unprecedented
characterization of the spatiotemporal dynamics of noradrenergic modulation.

## Key facts

- **NIH application ID:** 10537371
- **Project number:** 1F31NS129354-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Clayton Barnes
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10537371

## Citation

> US National Institutes of Health, RePORTER application 10537371, Spatiotemporal Dynamics of Noradrenergic Signaling in the Neocortex (1F31NS129354-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10537371. Licensed CC0.

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